2024
Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction
Rudokas M, McKay M, Toksoy Z, Eisen J, Bögner M, Young L, Akar F. Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction. Cardiovascular Diabetology 2024, 23: 261. PMID: 39026280, PMCID: PMC11264840, DOI: 10.1186/s12933-024-02357-1.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesMitochondrial network remodelingDamaged mitochondrial DNAEfficiency of oxidative phosphorylationImpaired ATP productionMitochondrial ultrastructural alterationsCardiac functionDiabetic heartCellular energy metabolismProduction of reactive oxygen speciesMitochondrial DNAMitochondrial networkMitochondrial fissionExcessive production of reactive oxygen speciesOxidative phosphorylationATP productionResponse to ischemic insultGlobal cardiac functionCell deathOverall cardiac functionCardiac ischemic injuryResponse to injuryCardiac mitochondriaIrreversible cell deathMitochondria
2016
Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart
Nederlof R, Gürel-Gurevin E, Eerbeek O, Xie C, Deijs GS, Konkel M, Hu J, Weber NC, Schumacher CA, Baartscheer A, Mik EG, Hollmann MW, Akar FG, Zuurbier CJ. Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart. Journal Of Physiology And Biochemistry 2016, 73: 323-333. PMID: 28258543, PMCID: PMC5534207, DOI: 10.1007/s13105-017-0555-3.Peer-Reviewed Original ResearchConceptsIschemia/reperfusionR injuryCardiac energeticsRecovery of functionHexokinase IISignificant LDH releasePossible underlying mechanismsIschemic insultCardiac recoveryControl heartsMtHKIIReperfusionIschemiaDHE fluorescenceRat heartR intervalLDH releasePeptide treatmentIntact heartInjuryUnderlying mechanismHeartMVO2NecrosisTreatment
2015
The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease
Motloch LJ, Hu J, Akar FG. The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease. Oxidative Medicine And Cellular Longevity 2015, 2015: 234104. PMID: 25918579, PMCID: PMC4397036, DOI: 10.1155/2015/234104.Peer-Reviewed Original ResearchConceptsIschemic heart diseaseHeart diseaseTranslocator proteinAcute ischemia-reperfusion injuryReactive oxygen speciesIschemia-reperfusion injuryMultiple organ systemsExcitation-contraction couplingMultiple cardiovascular disordersPermeability transition poreRole of TSPOMyocardial infarctionInflammatory processDiverse pathophysiological processesImmune responseCardiovascular disordersTherapeutic targetPathophysiological processesOrgan systemsDiagnostic markerMitochondrial dysfunctionDiseaseAbundant expressionMitochondrial translocator proteinROS release
2012
GSH or Palmitate Preserves Mitochondrial Energetic/Redox Balance, Preventing Mechanical Dysfunction in Metabolically Challenged Myocytes/Hearts From Type 2 Diabetic Mice
Tocchetti CG, Caceres V, Stanley BA, Xie C, Shi S, Watson WH, O’Rourke B, Spadari-Bratfisch RC, Cortassa S, Akar FG, Paolocci N, Aon MA. GSH or Palmitate Preserves Mitochondrial Energetic/Redox Balance, Preventing Mechanical Dysfunction in Metabolically Challenged Myocytes/Hearts From Type 2 Diabetic Mice. Diabetes 2012, 61: 3094-3105. PMID: 22807033, PMCID: PMC3501888, DOI: 10.2337/db12-0072.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 2GlucoseGlutathioneIsoproterenolMiceMitochondriaModels, BiologicalMuscle CellsOxidation-ReductionPalmitatesReactive Oxygen SpeciesConceptsMechanical dysfunctionReactive oxygen speciesType 2 diabetic db/db miceDiabetic db/db miceHigh glucoseType 2 diabetic patientsType 2 diabetic miceDb/db miceLower cardiac performanceLimited exercise capacityPoor glycemic controlType 2 diabetesΒ-agonist isoproterenolCardiac work demandsFatty acid palmitateExercise capacitySympathetic driveGlycemic controlDiabetic patientsDiabetic miceDb miceHeart dysfunctionPatient's inabilityMitochondrial reactive oxygen speciesHeart preparation
2010
A brighter side of ROS revealed by selective activation of β‐adrenergic receptor subtypes
Biary N, Akar FG. A brighter side of ROS revealed by selective activation of β‐adrenergic receptor subtypes. The Journal Of Physiology 2010, 588: 2973-2974. PMID: 20710039, PMCID: PMC2956937, DOI: 10.1113/jphysiol.2010.195743.Commentaries, Editorials and LettersAdrenergic beta-1 Receptor AgonistsAdrenergic beta-2 Receptor AgonistsAnimalsGTP-Binding Protein alpha Subunits, Gi-GoHomeostasisHumansMyocytes, CardiacNitric OxideNitric Oxide Synthase Type IIIOxygenRatsReactive Oxygen SpeciesReceptors, Adrenergic, beta-1Receptors, Adrenergic, beta-2Signal TransductionAltered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart
Jin H, Nass RD, Joudrey PJ, Lyon AR, Chemaly ER, Rapti K, Akar FG. Altered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart. Biophysical Journal 2010, 98: 2063-2071. PMID: 20483313, PMCID: PMC2872265, DOI: 10.1016/j.bpj.2010.01.045.Peer-Reviewed Original Research
2009
From mitochondrial dynamics to arrhythmias
Aon MA, Cortassa S, Akar FG, Brown DA, Zhou L, O’Rourke B. From mitochondrial dynamics to arrhythmias. The International Journal Of Biochemistry & Cell Biology 2009, 41: 1940-1948. PMID: 19703656, PMCID: PMC2732583, DOI: 10.1016/j.biocel.2009.02.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArrhythmias, CardiacHumansMembrane Potential, MitochondrialMembrane PotentialsMitochondria, HeartOxidative StressReactive Oxygen SpeciesConceptsWhole cellsMitochondrial membrane potentialMode of functionMitochondrial networkOxidative stressMitochondrial dynamicsReactive oxygen speciesMitochondrial criticalityMitochondria behaveMitochondriaCellular excitabilityOxygen speciesMembrane potentialPhysiological conditionsROSCatastrophic arrhythmiasCellsCardiac cellsEnergetic failureNormal conditionsSpeciesMessengerNADHStressBroad range
2005
The mitochondrial origin of postischemic arrhythmias
Akar FG, Aon MA, Tomaselli GF, O'Rourke B. The mitochondrial origin of postischemic arrhythmias. Journal Of Clinical Investigation 2005, 115: 3527-3535. PMID: 16284648, PMCID: PMC1280968, DOI: 10.1172/jci25371.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnionsArrhythmias, CardiacDose-Response Relationship, DrugElectrophysiologyGuinea PigsHeartIntracellular MembranesIon ChannelsIschemiaMembrane PotentialsMicroscopy, ConfocalMitochondria, HeartMyocardial IschemiaMyocardial ReperfusionMyocardial Reperfusion InjuryMyocardiumMyocytes, CardiacOscillometryReactive Oxygen SpeciesReceptors, GABA-AReperfusion InjuryTemperatureTime FactorsConceptsAction potentialsVentricular fibrillationPostischemic functional recoveryIschemic heart diseaseGuinea pig heartsNew therapeutic targetsAbnormal electrical activationPostischemic arrhythmiasReperfusion arrhythmiasFunctional recoveryGlobal ischemiaHeart diseaseBolus infusionArrhythmia preventionElectrophysiological changesAP shorteningControl heartsPostischemic heartsBenzodiazepine receptorsElectrophysiological substrateTherapeutic targetArrhythmiasReperfusionPig heartsMitochondrial benzodiazepine receptor